ꞵ3-adrenoceptor agonists, including mirabegron and vibegron, are used to manage urinary frequency and overactive bladder syndrome. This article outlines their mechanism of action, pharmacokinetics, cautions and contraindications, adverse effects, and clinically significant drug interactions. Mechanism of action During the urine storage phase, sympathetic nerve stimulation predominates. Noradrenaline is released and activates ꞵ-adrenoceptors in the bladder leading to smooth muscle relaxation and bladder filling. When the bladder is ready to void, parasympathetic stimulation occurs, releasing acetylcholine, which acts on muscarinic M2 and M3 receptors to cause bladder contraction. Mirabegron and vibegron are potent and selective ꞵ3-adrenoceptor agonists that relax detrusor smooth muscle, enhancing urine storage and reducing urgency and frequency of micturition. Created in BioRender. Boucher, M. (2025) https://BioRender.com/4j429gk Fig 1: Mirabegron is a selective β₃-adrenoceptor agonist that relaxes detrusor smooth muscle to increase bladder capacity. Pharmacokinetic Parameters The following table describes key pharmacokinetic parameters for ꞵ3-adrenoceptor agonists Parameter Mirabegron (Prolonged-Release Tablets) Vibegron Tmax 3–4 hours 1–3 hours Steady-State (Css) Reached within 7 days (once-daily dosing) Reached within 7 days Terminal Half-Life ≈ 50 hours 59–94 hours (in both young and elderly subjects) Metabolism CYP3A4, CYP2D6, butyrylcholinesterase, UGT, and possibly alcohol dehydrogenase (ADH) CYP3A4, UGT, and P-gp substrate; metabolism not a major elimination route Elimination Primarily renal and hepatic Mainly biliary/fecal excretion; minimal metabolism Cautions and Contraindications The following cautions and contraindications are applicable for mirabegron and vibegron: Cautions Bladder outlet obstruction and/or concomitant antimuscarinics – risk of urinary retention Congenital or acquired QT prolongation Contraindications Severe renal impairment (GFR <15 mL/min/1.73 m²) Severe hepatic impairment (Child-Pugh C) Additional contraindications for mirabegron: Mirabegron can increase blood pressure and is contraindicated in patients with severe uncontrolled hypertension (systolic ≥180 mmHg and/or diastolic ≥110 mmHg) Haemodialysis Moderate hepatic impairment with strong CYP3A4 inhibitors GFR 15–29 mL/min/1.73 m² with strong CYP3A4 inhibitors Additional contraindications for vibegron: Hereditary galactose intolerance, total lactase deficiency, or glucose–galactose malabsorption Adverse Effects Adverse Effect Mirabegron Vibegron Notes ↑ Blood pressure / Tachycardia ✅ ❌ Reversible upon discontinuation ↑ Liver enzymes (GGT, AST, ALT) ✅ ❌ Monitor if symptomatic Angioedema ✅ ❌ Rare, discontinue immediately UTI ✅ ✅ Common Headache ✅ ✅ Mild and transient Nausea / Diarrhoea ✅ ✅ Gastrointestinal effects generally mild Interactions Mirabegron Metabolised by CYP3A4: Strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, clarithromycin): reduce mirabegron dose in mild–moderate renal or hepatic impairment, avoid use in severe renal or moderate hepatic impairment. Inhibits CYP2D6: monitor for toxicity with CYP2D6 substrates with narrow therapeutic index (e.g. imipramine, desipramine, flecainide) Inhibits P-gp: P-gp substrates (e.g. digoxin): start digoxin at the lowest dose; monitor serum digoxin levels. Vibegron Substrate for CYP3A4, UGT enzymes and P-gp No dose adjustments required for CYP3A4 inducers or inhibitors – metabolism does not play a main role in elimination of vibegron and CYP3A4 is expected to have minimal involvement Vibegron has shown to increase levels of digoxin (P-gp substrate) – serum digoxin levels should be monitored Caution with vibegron and p-gp substrates with narrow therapeutic window (e.g. dabigatran, apixaban, rivaroxaban) References Mirabegron Astellas 25 mg prolonged-release tablets – Summary of Product Characteristics (SmPC) – (emc) Obgemsa 75 mg film-coated tablets – Summary of Product Characteristics (SmPC) – (emc) Do you think you’re ready? Take the quiz below Pro Feature - Quiz Beta-3-Adrenoceptor Agonists Question 1 of 3 Submitting... Skip Next Rate question: You scored 0% Skipped: 0/3 More Questions Available Upgrade to TeachMePharmacy Pro Challenge yourself with over 2100 multiple-choice questions to reinforce learning Learn More Rate This Article